tbuckley/cabot-search huggingface dataset:
Electrohydraulic lithotripsy for ball valve syndrome due to stent-stone complex after endoscopic ultrasound-guided hepaticogastrostomy
Authors: Moegi Mochizuki, Kenji Nakamura, Kyoko Arahata, Sakiko Takarabe, Hiroshi Kishikawa, Tadakazu Hisamatsu, Jiro Nishida
Journal: Endoscopy (2023)

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is the standard endoscopic procedure for malignant biliary obstruction [1] [2]. However, the rate of EUS-HGS-associated adverse events remains high, and various severe complications, including risk factor and rescue techniques, have been reported [3] [4] [5]. We present a rare case of electrohydraulic lithotripsy (EHL) for ball valve syndrome due to a stent-stone complex after EUS-HGS.
Pre-emptive iron supplementation prevents myocardial iron deficiency and attenuates adverse remodelling after myocardial infarction
Authors: Bomee Chung, Yong Wang, Marleen Thiel, Fatemeh Rostami, Anika Rogoll, Valentin G Hirsch, Zulaikha Malik, Anne Bührke, Christian Bär, Michael Klintschar, Jan D Schmitto, Carla Vogt, Christopher Werlein, Danny Jonigk, Johann Bauersachs, Kai C Wollert, Tibor Kempf
Journal: Cardiovascular Research (2023)

Heart failure (HF) after myocardial infarction (MI) is a major cause of morbidity and mortality. We sought to investigate the functional importance of cardiac iron status after MI and the potential of pre-emptive iron supplementation in preventing cardiac iron deficiency (ID) and attenuating left ventricular (LV) remodelling.MI was induced in C57BL/6J male mice by left anterior descending coronary artery ligation. Cardiac iron status in the non-infarcted LV myocardium was dynamically regulated after MI: non-haem iron and ferritin increased at 4 weeks but decreased at 24 weeks after MI. Cardiac ID at 24 weeks was associated with reduced expression of iron-dependent electron transport chain (ETC) Complex I compared with sham-operated mice. Hepcidin expression in the non-infarcted LV myocardium was elevated at 4 weeks and suppressed at 24 weeks. Hepcidin suppression at 24 weeks was accompanied by more abundant expression of membrane-localized ferroportin, the iron exporter, in the non-infarcted LV myocardium. Notably, similarly dysregulated iron homeostasis was observed in LV myocardium from failing human hearts, which displayed lower iron content, reduced hepcidin expression, and increased membrane-bound ferroportin. Injecting ferric carboxymaltose (15 µg/g body weight) intravenously at 12, 16, and 20 weeks after MI preserved cardiac iron content and attenuated LV remodelling and dysfunction at 24 weeks compared with saline-injected mice.We demonstrate, for the first time, that dynamic changes in cardiac iron status after MI are associated with local hepcidin suppression, leading to cardiac ID long term after MI. Pre-emptive iron supplementation maintained cardiac iron content and attenuated adverse remodelling after MI. Our results identify the spontaneous development of cardiac ID as a novel disease mechanism and therapeutic target in post-infarction LV remodelling and HF.
Cardiomuscular Biomarkers in the Diagnosis and Prognostication of Immune Checkpoint Inhibitor Myocarditis
Authors: Lorenz H. Lehmann, Markus B. Heckmann, Guillaume Bailly, Daniel Finke, Adrien Procureur, John R. Power, Frederic Stein, Marie Bretagne, Stephane Ederhy, Charlotte Fenioux, Omar Hamwy, Elisa Funck-Brentano, Emanuela Romano, Laurence Pieroni, Jan P. Münster, Yves Allenbach, Céline Anquetil, Sarah Leonard-Louis, Nicolas L. Palaskas, Salim S. Hayek, Hugo A. Katus, Evangelos Giannitsis, Norbert Frey, Ziya Kaya, Javid Moslehi, Edi Prifti, Joe-Elie Salem, Franck Thuny, Shanthini Crusz, Aarti Asnani, Anja Karlstaedt, Fanny Rocher, Elise Paven, Michel Obeid, Wei Ting Chan, Danette L Flint, Dimitri Arangalage, Pierre-Yves Courand, Martin Nicol, Eve Cariou, Yuichi Tamura, Roberta Florido, Sanjeev Francis, Darryl Leong, Nicolas Piriou, Nausheen Akhter, Sandhu Shahneen, Osnat Itzhaki Ben Zadok, Manhal Habib, Pankit Vachhani, Giovanni Peretto, Han Zhu, Michal Laufer Perl, Mandar Aras, Joachim Alexandre, Carrie Lenneman, Joshua Levenson, Anita Deswal, Vlad G. Zaha, Elizabeth M Gaughan, Steven Ewer, Douglas Johnson, Lauren A Baldassarre
Journal: Circulation (2023)

Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established.
An Updated Report on the Prevalence of Prior Cancer Among Persons Newly Diagnosed With Cancer in the Surveillance, Epidemiology, and End Results Program
Authors: Caitlin C. Murphy, Guillermo A. Tortolero, David E. Gerber, Sandi L. Pruitt
Journal: JAMA Oncology (2023)

This cohort study uses population-based data from the National Cancer Institute Surveillance, Epidemiology, and End Results program of cancer registries to estimate prevalence of prior cancer among adults diagnosed with an incident cancer in 2019.
Association between a hospitalization for heart failure and the initiation/discontinuation of guideline‐recommended treatments: An analysis from the <scp>Swedish</scp> Heart Failure Registry
Authors: Benedikt Schrage, Lars H. Lund, Lina Benson, Frieder Braunschweig, João Pedro Ferreira, Ulf Dahlström, Marco Metra, Giuseppe M.C. Rosano, Gianluigi Savarese
Journal: European Journal of Heart Failure (2023)

Aims To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline‐directed medical HF therapy (GDMT) and consequent outcomes. Methods and results Among patients in the Swedish HF registry with an ejection fraction &lt;50% enrolled in 2009–2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1–4.0 vs. 1.4–1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1–44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin–angiotensin system inhibitors/angiotensin receptor–neprilysin inhibitors or beta‐blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists. Conclusions Following a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re‐/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re‐/initiation of GDMT following a HF hospitalization.
Innovative platforms for data aggregation, linkage and analysis in the context of pandemic and epidemic intelligence
Authors: Beth Blauer, John S Brownstein, Lauren Gardner, Moritz UG Kraemer, Zoila Beatriz Leiva Rioja, Edouard Mathieu, Isabel Redies, Oliver W Morgan
Journal: Eurosurveillance (2023)

During the COVID-19 pandemic, open-access platforms that aggregate, link and analyse data were transformative for global public health surveillance. This perspective explores the work of three of these platforms: Our World In Data (OWID), Johns Hopkins University (JHU) COVID-19 Dashboard (later complemented by the Coronavirus Resource Center), and Global.Health, which were presented in the second World Health Organization (WHO) Pandemic and Epidemic Intelligence Innovation Forum. These platforms, operating mostly within academic institutions, added value to public health data that are collected by government agencies by providing additional real-time public health intelligence about the spread of the virus and the evolution of the public health emergency. Information from these platforms was used by health professionals, political decision-makers and members of the public alike. Further engagement between government and non-governmental surveillance efforts can accelerate the improvements needed in public health surveillance overall. Increasing the diversity of public health surveillance initiatives beyond the government sector comes with several benefits: technology innovation in data science, engagement of additional highly skilled professionals, greater transparency and accountability for government agencies, and new opportunities to engage with members of society.
Thematic Analysis of State Medicaid Buprenorphine Prior Authorization Requirements
Authors: Max Jordan Nguemeni Tiako, Abby Dolan, Matthew Abrams, Kehinde Oyekanmi, Zachary Meisel, Shoshana V. Aronowitz
Journal: JAMA Network Open (2023)

Importance Prior authorization (PA) requirements for buprenorphine are associated with lower provision of the medication for the treatment of opioid use disorder (OUD). While Medicare plans have eliminated PA requirements for buprenorphine, many Medicaid plans continue to require them. Objective To describe and classify buprenorphine coverage requirements based on thematic analysis of state Medicaid PA forms. Design, Setting, and Participants This qualitative study used a thematic analysis of 50 states’ Medicaid PA forms for buprenorphine between November 2020 and March 2021. Forms were obtained from the jurisdiction’s Medicaid websites and assessed for features suggesting barriers to buprenorphine access. A coding tool was developed based on a review of a sample of forms, including fields for behavioral health treatment recommendations or mandates, drug screening requirements, and dosage limitations. Main Outcomes and Measures Outcomes included PA requirements for different buprenorphine formulations. Additionally, PA forms were evaluated for various criteria such as behavioral health, drug screenings, dose-related recommendations or mandates or patient education. Results Among the total of 50 US states in the analysis, most states’ Medicaid plans required PA for at least 1 formulation of buprenorphine. However, the majority did not require a PA for buprenorphine-naloxone. Four key themes of coverage requirements were identified: restrictive surveillance (eg, requirements for urine drug screenings, random drug screenings, pill counts), behavioral health treatment recommendations or mandates (eg, mandatory counseling or 12-step meeting attendance), interfering with or restricting medical decision-making (eg, maximum daily dosages of 16 mg, requiring additional steps for dosages higher than 16 mg), and patient education (eg, information about adverse effects and interactions with other medications). Eleven states (22%) required urine drug screenings, 6 states (12%) required random urine drug screenings, and 4 states (8%) required pill counts. Fourteen states’ forms (28%) recommended therapy, and 7 (14%) required therapy, counseling, or participation in group sessions. Eighteen states (36%) specified dosage maximums; among them, 11 (22%) required additional steps for a daily dosage higher than 16 mg. Conclusion In this qualitative study of state Medicaid PA requirements for buprenorphine, themes were identified that included patient surveillance with drug screenings and pill counts, behavioral health treatment recommendations or mandates, patient education, and dosing guidance. These results suggest that state Medicaid plans’ buprenorphine PA requirements for OUD are in conflict with existing evidence and may negatively affect states’ efforts to address the opioid overdose crisis.
Effective nose-to-brain drug delivery using a combination system targeting the olfactory region in monkeys
Authors: Keita Sasaki, Shota Fukakusa, Yusuke Torikai, Chie Suzuki, Ikumi Sonohata, Takuto Kawahata, Yasuhiro Magata, Keiichi Kawai, Shunji Haruta
Journal: Journal of Controlled Release (2023)

The nose-to-brain (N2B) pathway has garnered attention because it transports drugs directly into the brain. Although recent studies have suggested the necessity of selective drug administration to the olfactory region for effective N2B drug delivery, the importance of delivering the formulation to the olfactory region and the detailed pathway involved in drug uptake in primates brain remain unclear. Here, we developed a combination system for N2B drug delivery comprising a proprietary mucoadhesive powder formulation and a dedicated nasal device (N2B-system) and evaluated it for nasal drug delivery to the brain in cynomolgus monkeys. This N2B-system demonstrated a much greater formulation distribution ratio in the olfactory region in an in vitro experiment using a 3D-printed nasal cast and in vivo experiment using cynomolgus monkeys, as compared to that in other nasal drug delivery systems that comprise of a proprietary nasal powder device developed for nasal absorption and vaccination and a commercially available liquid spray. Additionally, Texas Red-labeled dextran (TR-DEX, 3 kDa) was administered using the N2B-system to estimate the drug transition pathway from the nasal cavity to the brain. TR-DEX preferentially localized to the olfactory epithelium and reached the olfactory bulb through the cribriform foramina. Moreover, domperidone, a model drug with poor blood-brain barrier permeability, was administered to assess the brain uptake of medicine after olfactory region-selective administration by using the N2B-system. Domperidone accumulation in the brain was evaluated using positron emission tomography with intravenously administered [18F]fallypride based on competitive inhibition of the dopamine D2 receptor (D2R). Compared to other systems, the N2B-system significantly increased D2R occupancy and domperidone uptake in the D2R-expressing brain regions. The current study reveals that the olfactory region of the nasal cavity is a suitable target for efficient nasal drug delivery to the brain in cynomolgus monkeys. Thus, the N2B-system, which targets the olfactory region, provides an efficient approach for developing effective technology for nasal drug delivery to the brain in humans.
Oral Delivery of Transformable Bilirubin Self‐Assembled System for Targeted Therapy of Colitis
Authors: Zhejie Chen, Yi Chen, Wei Hao, Mingju Shui, Jinming Zhang, Hefeng Zhou, Chen Zhang, Yitao Wang, Shengpeng Wang
Journal: Advanced Healthcare Materials (2023)

Ulcerative colitis (UC) is a high incidence disease worldwide and clinically presents as relapsing and incurable inflammation of the colon. Bilirubin (BR), a natural antioxidant with significant anti-colitic effects, is utilized in preclinical studies as an intestinal disease therapy. Due to their water-insolubility, the design of BR-based agents usually involves complicated chemosynthetic processes, introducing various uncertainties in BR development. After screening numerous materials, it is identified that chondroitin sulfate can efficiently mediate the construction of BR self-assembled nanomedicine (BSNM) via intermolecular hydrogen bonds between dense sulfate and carboxyl of chondroitin sulfate and imino groups of BR. BSNM exhibits pH sensitivity and reactive oxygen species responsiveness, enabling targeted delivery to the colon. After oral administration, BSNM significantly inhibits colonic fibrosis and apoptosis of colon and goblet cells; it also reduces the expression of inflammatory cytokines. Moreover, BSNM maintains the normal level of zonula occludens-1 and occludin to sustain the integrity of intestinal barrier, regulates the macrophage polarization from M1 to M2 type, and promotes the ecological recovery of intestinal flora. Collectively, the work provides a colon-targeted and transformable BSNM that is simple to prepare and is useful as an efficient targeted UC therapy.
<scp><i>NPM1</i></scp>‐mutated acute myeloid leukemia: New pathogenetic and therapeutic insights and open questions
Authors: Brunangelo Falini
Journal: American Journal of Hematology (2023)

Abstract The nucleophosmin ( NPM1 ) gene encodes for a multifunctional chaperone protein that is localized in the nucleolus but continuously shuttles between the nucleus and cytoplasm. NPM1 mutations occur in about one‐third of AML, are AML‐specific, usually involve exon 12 and are frequently associated with FLT3 ‐ITD, DNMT3A, TET2 , and IDH1/2 mutations. Because of its unique molecular and clinico‐pathological features, NPM1 ‐mutated AML is regarded as a distinct leukemia entity in both the International Consensus Classification (ICC) and the 5th edition of the World Health Organization (WHO) classification of myeloid neoplasms. All NPM1 mutations generate leukemic mutants that are aberrantly exported in the cytoplasm of the leukemic cells and are relevant to the pathogenesis of the disease. Here, we focus on recently identified functions of the NPM1 mutant at chromatin level and its relevance in driving HOX/MEIS gene expression. We also discuss yet controversial issues of the ICC/WHO classifications, including the biological and clinical significance of therapy‐related NPM1 ‐mutated AML and the relevance of blasts percentage in defining NPM1 ‐mutated AML. Finally, we address the impact of new targeted therapies in NPM1 ‐mutated AML with focus on CAR T cells directed against NPM1/HLA neoepitopes, as well as XPO1 and menin inhibitors.
Hypoxaemia in patients with heart failure and preserved ejection fraction
Authors: Massar Omar, Kazunori Omote, Hidemi Sorimachi, Dejana Popovic, Ardaas Kanwar, Alessio Alogna, Yogesh N.V. Reddy, Kaiser G. Lim, Sanjiv J. Shah, Barry A. Borlaug
Journal: European Journal of Heart Failure (2023)
Gut microbiota changes associated with <i>Clostridioides difficile</i> infection and its various treatment strategies
Authors: Anne J. Gonzales-Luna, Travis J. Carlson, Kevin W. Garey
Journal: Gut Microbes (2023)

Human gut microbiota are critical to both the development of and recovery from Clostridioides difficile infection (CDI). Antibiotics are the mainstay of CDI treatment, yet inherently cause further imbalances in the gut microbiota, termed dysbiosis, complicating recovery. A variety of microbiota-based therapeutic approaches are in use or in development to limit disease- and treatment-associated dysbiosis and improve rates of sustained cure. These include the recently FDA-approved fecal microbiota, live-jslm (formerly RBX2660) and fecal microbiota spores, live-brpk (formerly SER−109), which represent a new class of live biotherapeutic products (LBPs), traditional fecal microbiota transplantation (FMT), and ultra-narrow-spectrum antibiotics. Here, we aim to review the microbiome changes associated with CDI as well as a variety of microbiota-based treatment approaches.
Systemic exposure to bacterial amyloid curli alters the gut mucosal immune response and the microbiome, exacerbating <i>Salmonella</i> -induced arthritis
Authors: Shingo Bessho, Kaitlyn C. M. Grando, Kathrine Kyrylchuk, Amanda Miller, Andres J. Klein-Szanto, Wenhan Zhu, Stefania Gallucci, Vincent Tam, Çagla Tükel
Journal: Gut Microbes (2023)

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Rest and exercise early after sport-related concussion: a systematic review and meta-analysis
Authors: John J Leddy, Joel S Burma, Clodagh M Toomey, Alix Hayden, Gavin A Davis, Franz E Babl, Isabelle Gagnon, Christopher C Giza, Brad G Kurowski, Noah D Silverberg, Barry Willer, Paul E Ronksley, Kathryn J Schneider
Journal: British Journal of Sports Medicine (2023)

Objective To synthesise the evidence regarding the risks and benefits of physical activity (PA), prescribed aerobic exercise treatment, rest, cognitive activity and sleep during the first 14 days after sport-related concussion (SRC). Design Meta-analysis was performed for PA/prescribed exercise interventions and a narrative synthesis for rest, cognitive activity and sleep. Risk of bias (ROB) was determined using the Scottish Intercollegiate Guidelines Network and quality assessed using Grading of Recommendations, Assessment, Development and Evaluations. Data sources MEDLINE, Embase, APA PsycInfo, Cochrane Central Register of Controlled Trials, CINAHL Plus and SPORTDiscus. Searches were conducted in October 2019 and updated in March 2022. Eligibility criteria Original research articles with sport-related mechanism of injury in &gt;50% of study sample and that evaluated how PA, prescribed exercise, rest, cognitive activity and/or sleep impact recovery following SRC. Reviews, conference proceedings, commentaries, editorials, case series, animal studies and articles published before 1 January 2001 were excluded. Results 46 studies were included and 34 had acceptable/low ROB. Prescribed exercise was assessed in 21 studies, PA in 15 studies (6 PA/exercise studies also assessed cognitive activity), 2 assessed cognitive activity only and 9 assessed sleep. In a meta-analysis of seven studies, PA and prescribed exercise improved recovery by a mean of −4.64 days (95% CI −6.69, –2.59). After SRC, early return to light PA (initial 2 days), prescribed aerobic exercise treatment (days 2–14) and reduced screen use (initial 2 days) safely facilitate recovery. Early prescribed aerobic exercise also reduces delayed recovery, and sleep disturbance is associated with slower recovery. Conclusion Early PA, prescribed aerobic exercise and reduced screen time are beneficial following SRC. Strict physical rest until symptom resolution is not effective, and sleep disturbance impairs recovery after SRC. PROSPERO registration number CRD42020158928.